CA2436724A1 - Use of inhibitors of dipeptidyl peptidase iv (dp iv) in combination with inhibitors of alanyl-aminopeptidase (apn) - Google Patents

Use of inhibitors of dipeptidyl peptidase iv (dp iv) in combination with inhibitors of alanyl-aminopeptidase (apn) Download PDF

Info

Publication number
CA2436724A1
CA2436724A1 CA002436724A CA2436724A CA2436724A1 CA 2436724 A1 CA2436724 A1 CA 2436724A1 CA 002436724 A CA002436724 A CA 002436724A CA 2436724 A CA2436724 A CA 2436724A CA 2436724 A1 CA2436724 A1 CA 2436724A1
Authority
CA
Canada
Prior art keywords
inhibitors
xaa
apn
aminopeptidase
enzymes
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002436724A
Other languages
French (fr)
Other versions
CA2436724C (en
Inventor
Siegfried Ansorge
Uwe Lendeckel
Klaus Neubert
Dirk Reinhold
Robert Vetter
Harald Gollnick
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
IMTM GmbH
Original Assignee
Siegfried Ansorge
Uwe Lendeckel
Klaus Neubert
Dirk Reinhold
Robert Vetter
Harald Gollnick
Institut Fur Medizintechnologie Magdeburg (Imtm) Gmbh
Imtm Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from DE2001100052 external-priority patent/DE10100052A1/en
Priority claimed from DE2001102392 external-priority patent/DE10102392A1/en
Priority claimed from DE2001155093 external-priority patent/DE10155093A1/en
Application filed by Siegfried Ansorge, Uwe Lendeckel, Klaus Neubert, Dirk Reinhold, Robert Vetter, Harald Gollnick, Institut Fur Medizintechnologie Magdeburg (Imtm) Gmbh, Imtm Gmbh filed Critical Siegfried Ansorge
Priority to CA002627862A priority Critical patent/CA2627862C/en
Publication of CA2436724A1 publication Critical patent/CA2436724A1/en
Application granted granted Critical
Publication of CA2436724C publication Critical patent/CA2436724C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/55—Protease inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/05—Dipeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/06—Tripeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/55—Protease inhibitors
    • A61K38/556—Angiotensin converting enzyme inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Vascular Medicine (AREA)
  • Pulmonology (AREA)
  • Dermatology (AREA)
  • Urology & Nephrology (AREA)
  • Transplantation (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Cardiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

The invention relates to the use of inhibitors of dipeptidyl peptidase IV (D P IV) and enzymes having the same specific nature of substrate (DP IV enzyme activity), combined with inhibitors of alanyl aminopeptidase (aminopeptidase N, APN), or enzymes having the same specific nature of substrate (APN enzyme activity), for the additive to superadditive inhibition of the activation an d proliferation (DNS synthesis) of human T lymphocytes or mononuclear cells an d of the production of TH2 cytokines for the treatment and prevention of allergic reactions of type I according to the Gell and Coombs classification , for the additive to superadditive inhibition of the activation and proliferation (DNS synthesis) of human epidermal and follicular keratinocyte s and those of the transitional region between the skin and the mucosa, and fo r the treatment and prevention of dermatological diseases associated with follicular and epidermal hyperkeratosis and reinforced keratinocyte proliferation. The invention also relates to the use of inhibitors of dipeptidyl peptidase IV (DP IV) and enzymes having the same specific nature of substrate (DP IV enzyme activity), combined with inhibitors of alanyl aminopeptidase (aminopeptidase N, APN), or enzymes having the same specific nature of substrate (APN enzyme activity), inhibitors of X-pro-aminopeptidas e (aminopeptidase P, APP), inhibitors of the angiotensin-converting enzyme (AC E) and/or of prolyoligopeptidase (POP, prolylendopeptidase, PEP) for the additi ve to superadditive inhibition of the activation, DNS synthesis and proliferati on of human T lymphocytes or mononuclear cells for the treatment and prophylaxi s of arteriosclerosis. The invention further relates to pharmaceutical preparations comprising a plurality of inhibitors of enzymes of the above- mentioned groups.

Claims (23)

1. Use of inhibitors of dipeptidyl peptidase IV (DP IV) as well as of enzymes having the same substrate specifity (DP IV-analogous enzymatic activity) in combination with inhibitors of alanyl-aminopeptidase (aminopeptidase N, APN) and of enzymes having the same substrate specifity (APN-analogous enzymatic activity), respec-tively, for a more than additive to superadditive inhibition of the activation and pro-liferation (DNA-synthesis) of human T lymphocytes and mononuclear cells, respec-tively, and the production of T H2 cytokines.
2. Use of inhibitors of dipeptidyl peptidase IV (DP IV) as well as of enzymes having the same substrate specifity (DP IV-analogous enzymatic activity) in combination with inhibitors of alanyl aminopeptidase (aminopeptidase N, APN) and of enzymes having the same substrate specifity (APN-analogous enzymatic activity), respec-tively, for a more than additive to superadditive inhibition of activation and prolif-eration (DNA-synthesis) of human epidermal and follicular keratinocytes as well as keratinocytes of the transition zone from the skin to mucous membranes.
3. Use of inhibitors of dipeptidyl peptidase IV (DP IV) as well as of enzymes having the same substrate specifity (DP IV-analogous enzymatic activity) in combination with inhibitors of alanyl aminopeptidase (aminopeptidase N, APN) and of enzymes having the same substrate specifity (APN-analogous enzymatic activity), respec-tively, of X-Pro-aminopeptidase (aminopeptidase P, APP), of the "angiotensin-converting enzyme" (ACE) and/or of the prolyl oligopeptidase (POP, prolyl endo-peptidase, PEP) for a more than additive to superadditive inhibition of activation, DNA synthesis and proliferation of human T lymphocytes and mononuclear cells.
4. Use according to any of the claims 1 to 3 wherein the inhibitors of DP IV
are Xaa-Pro-dipeptides (Xaa = .alpha.-amino acid and side chain protected derivative, respec-tively), corresponding derivatives, preferably dipeptide phosphonic acid diaryl es-ters, dipeptide boronic acids (e. g. Pro-boro-Pro) and their salts, Xaa-Xaa-(Trp)-Pro-(Xaa)n peptides (Xaa = .alpha.-amino acid, n = 0 to 10), corresponding derivatives and their salts and amino acid-(Xaa)-amides, respectively, corresponding derivatives and their salts, wherein Xaa is an .alpha.-amino acid or a side chain protected derivative, re-spectively, preferably N~-4-nitrobenzyloxycarbonyl-L-lysine, L-proline, L-trypto-phane, L-isoleucine, L-valine, and cyclic amines as, for example, pyrrolidine, pi-peridine, thiazolidine, and their derivatives serve as the amide structure.
5. Use according to any of the claims 1 to 4, wherein amino acid amides, e. g.
N~-4-nitrobenzyloxycarbonyl-L-lysine thiazolidide, pyrrolidide and piperidide as well as the corresponding 2-cyanothiazolidide, 2-cyanopyrrolidide and 2-cyanopiperidide derivative are used as DP IV inhibitors.
6. Use according to claim 1, wherein, as the inhibitors of APN, actinoine, leuhistine, phebestine, amastatine, bestatine, probestine, .beta.-aminothiols, .alpha.-aminophosphinic acids, .alpha.-aminophosphinic acid derivatives, preferably D-Phe-.psi.[PO(OH)-CH2]-Phe-Phe and their salts, are used.
7. Use according to claim 3, wherein, as the inhibitors of APP, there are used apstatine, (2S,3R)-HAMH-L-proline, (2S,3R)-HAPB-L-proline, the corresponding L-proline methyl ester, (2S,3R)-HAMH-/(2S,3R)-HAPB-pyrrolidides, thiazolidides (HAMH =
3-amino-2-hydroxy-5-methyl-hexanoyl, HAPB = 3-amino-2-hydroxy-4-phenyl-butanoyl) and their salts.
8. Use according to claim 3 or claim 7, wherein, as the inhibitors of ACE, captopril, enalapril, lisinopril, cilazopril and their salts are used.
9. Use according to any of the claims 3, 7 or 8, wherein, as the inhibitors of POP
(PEP), there are used postatin, eurystatin A or B, N a-protected peptide aldehydes, preferably benzyloxycarbonyl-L-prolyl-L-prolinal and benzyloxycarbonyl-L-thio-prolyl-L-thioprolinal, N a-protected amino acid-(Xaa) pyrrolidides or thiazolidides (Xaa = .alpha.-amino acid, preferably L-alanine, L-valine, L-isoleucine) as well as the corresponding 2-cyanopyrrolidide and 2-cyanothiazolidide derivatives, substrate-analogous N a-protected peptide phosphonic acid diaryl esters and peptide di-azomethyl ketones and peptide ammonium methyl ketones, respectively, and their salts.
10. Use of inhibitor combinations according to any of the claims 1 and 4 to 9 for a pre-vention and therapy of chronic diseases having an inflammatory genesis, as auto-immune diseases and arteriosclerosis.
11. Use of inhibitor combinations according to any of the claims 1 and 4 to 6 for a pre-vention and therapy of allergic reactions of the type I.
12. Use of the inhibitor combinations according to any of the claims 1, 2 and 4 to 6 for a prevention and therapy of inflammatory and non-inflammatory epidermal hyperpro-liferation conditions (e. g. congenital ichthyoses and psoriasis), benign and malign epidermal clonal expansions (e. g. warts, condylomes, actinic keratoses/precancer-oses), benign and malign hyperproliferation conditions (e. g. keratosis follicularis) as well as benign and malign epithelial adnex tumors and primary and reactive nail cell hyperproliferations.
13. Pharmaceutical preparations, comprising inhibitors of dipeptidyl peptidase IV (DP
IV) or of enzymes having a DP IV-analogous enzymatic activity, in combination with inhibitors of one of the enzymes alanyl aminopeptidase (aminopeptidase N, APN) and inhibitors of enzymes having the same substrate specifity (APN-analogous enzymatic activity) and in combination with per se known carriers, addi-tives and/or auxiliary substances.
14. Pharmaceutical preparations, comprising inhibitors of dipeptidyl peptidase IV (DP
IV) or of enzymes having a DP IV-analogous enzymatic activity, in combination with inhibitors of one of the enzymes alanyl aminopeptidase (aminopeptidase N, APN) and inhibitors of enzymes having the same substrate specifity (APN-analogous enzymatic activity), of X-Pro-aminopeptidase (aminopeptidase P, APP), of the "angiotensin-convening enzyme" (ACE) and prolyl oligopeptidase (POP, prolylendopeptidase, PEP) and in combination with per se known carriers, additives and/or auxiliary substances.
15. Pharmaceutical preparations according to claim 13 or claim 14, comprising, as in-hibitors of DP IV, preferably Xaa-Pro dipeptides (Xaa = .alpha.- amino acid and side chain protected derivative, respectively), corresponding derivatives, preferably di-peptide phosphonic acid diaryl esters, dipeptide boronic acids (e. g. Pro-boro-Pro) and their salts, Xaa-Xaa-(Trp)-Pro-(Xaa)n peptides (Xaa = .alpha.-amino acid, n = 0 to 10), corresponding derivatives and their salts and amino acid-(Xaa) amides, corre-sponding derivatives and their salts, respectively, wherein Xaa is an .alpha.-amino acid or a side chain protected derivative respectively, preferably N.epsilon.-4-nitrobenzyloxy-carbonyl-L-lysine, L-proline, L-tryptophane, L-isoleucine, L-valine, and cyclic amines as, for example, pyrrolidine, piperidine, thiazolidine, and their derivatives serve as the amide structure.
16. Pharmaceutical preparations according to claim 13, 14 or 15, comprising, as inhibi-tors of DP IV, amino acid amides, e. g. N~-4-nitrobenzyloxycarbonyl-L-lysine-thiazolidide, pyrrolidide and piperidide as well as the corresponding 2-cyanothiazolidide, 2-cyanopyrrolidide and 2-cyanopiperidide derivative.
17. Pharmaceutical preparations according to any of the claims 13 to 16, comprising as inhibitors of APN, actinoine, leuhistine, phebestine, amastatine, bestatine, probes-tine, .beta.-aminothiols, .alpha.-aminophosphinic acids, .alpha.-aminophosphinic acid derivatives, preferably D-Phe-.psi.[PO(OH)-CH2]-Phe-Phe and their salts.
18. Pharmaceutical preparations according to any of the claims 14 to 17, comprising, as inhibitors of APP, apstatine, (2S,3R)-HAMH-L-proline, (2S,3R)-HAPB-L-proline, the corresponding L-proline methyl ester, (2S,3R)-HAMH-/(2S,3R)-HAPB-pyrroli-dides, thiazolidides (HAMH = 3-amino-2-hydroxy-5-methyl-hexanoyl, HAPB = 3-amino-2-hydroxy-4-phenyl-butanoyl) and their salts.
19. Pharmaceutical preparations according to any of the claims 14 to 18, comprising as inhibitors of ACE captopril, enalapril, lisinopril, cilazopril and their salts.
20. Pharmaceutical preparations according to any of the claims 14 to 19, comprising as inhibitors of POP (PEP) preferably postatin, eurystatin A or B, N a-protected pep-tidaldehydes, preferably benzyloxycarbonyl-L-prolyl-L-prolinal and benzyloxycar-bonyl-L-thioprolyl-L-thioprolinal, N a-protected amino acid-(Xaa) pyrrolidides or thiazolidides (Xaa = .alpha.-amino acid, preferably L-alanine, L-valine, L-isoleucine) as well as the corresponding 2-cyanopyrrolidide and 2-cyanothiazolidide derivatives, substrate-analogous N a-protected peptide phosphonic acid diaryl esters and peptide diazomethyl ketones and peptide ammonium methyl ketones, respectively, and their salts.
21. Pharmaceutical preparations according to any of the claims 14 to 20, comprising two or more inhibitors of DP IV or of enzymes of DP IV-analogous enzymatic ac-tivity of APN or of enzymes having APN-analogous enzymatic activity, of ACE, of POP (PEP) and of XPNPEP2 in a compartimentally separate formulation in combi-nation with per se known carrier, auxiliary and/or additive substances for a simulta-neous or immediately timely consecutive administration with the aim of a combined effect.
22. Pharmaceutical preparations according to any of the claims 13 to 21 for the systemic application for an oral, transdermal, intravenous, subcutaneous, intracutaneous, in-tramuscular, rectal, vaginal, sublingual administration together with per se known carrier, auxiliary and/or additive substances.
23. Pharmaceutical preparations according to any of the claims 13 to 21 for the topical application in the form of, for example, creams, ointments, pastes, gels, solutions, sprays, liposomes, shaken mixtures, hydro-colloid dressings and other dermatolog-ical bases/vehicles including instillative applications.
CA2436724A 2001-01-02 2001-12-21 Use of inhibitors of dipeptidyl peptidase iv (dp iv) in combination with inhibitors of alanyl-aminopeptidase (apn) Expired - Fee Related CA2436724C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CA002627862A CA2627862C (en) 2001-01-02 2001-12-21 Use of inhibitors of dipeptidyl peptidase iv (dp iv) in combination with inhibitors of alanyl-aminopeptidase (apn)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
DE10100052.9 2001-01-02
DE2001100052 DE10100052A1 (en) 2001-01-02 2001-01-02 Inhibiting DNA synthesis in T-lymphocytes, keratinocytes and TH2 cytokine production, comprises combined administration of dipeptidyl peptidase and alanyl-aminopeptidase inhibitors
DE2001102392 DE10102392A1 (en) 2001-01-19 2001-01-19 Inhibiting DNA synthesis in T-lymphocytes, keratinocytes and TH2 cytokine production, comprises combined administration of dipeptidyl peptidase and alanyl-aminopeptidase inhibitors
DE10102392.8 2001-01-19
DE10155093.6 2001-11-09
DE2001155093 DE10155093A1 (en) 2001-11-09 2001-11-09 Inhibiting DNA synthesis in T-lymphocytes, keratinocytes and TH2 cytokine production, comprises combined administration of dipeptidyl peptidase and alanyl-aminopeptidase inhibitors
PCT/EP2001/015199 WO2002053170A2 (en) 2001-01-02 2001-12-21 Combined use of enzyme inhibitors and pharmaceutical preparations thereof for the treatment and prophylaxis of arteriosclerosis, for the treatment and prevention of allergic reactions of type i according to the gell and coombs classification, and for the treatment and prevention of dermatological diseases associated with fo

Related Child Applications (1)

Application Number Title Priority Date Filing Date
CA002627862A Division CA2627862C (en) 2001-01-02 2001-12-21 Use of inhibitors of dipeptidyl peptidase iv (dp iv) in combination with inhibitors of alanyl-aminopeptidase (apn)

Publications (2)

Publication Number Publication Date
CA2436724A1 true CA2436724A1 (en) 2002-07-11
CA2436724C CA2436724C (en) 2010-03-16

Family

ID=27214230

Family Applications (2)

Application Number Title Priority Date Filing Date
CA002627862A Expired - Fee Related CA2627862C (en) 2001-01-02 2001-12-21 Use of inhibitors of dipeptidyl peptidase iv (dp iv) in combination with inhibitors of alanyl-aminopeptidase (apn)
CA2436724A Expired - Fee Related CA2436724C (en) 2001-01-02 2001-12-21 Use of inhibitors of dipeptidyl peptidase iv (dp iv) in combination with inhibitors of alanyl-aminopeptidase (apn)

Family Applications Before (1)

Application Number Title Priority Date Filing Date
CA002627862A Expired - Fee Related CA2627862C (en) 2001-01-02 2001-12-21 Use of inhibitors of dipeptidyl peptidase iv (dp iv) in combination with inhibitors of alanyl-aminopeptidase (apn)

Country Status (8)

Country Link
US (2) US7229969B2 (en)
EP (1) EP1349576B1 (en)
JP (1) JP2004520330A (en)
CN (1) CN100579582C (en)
AT (1) ATE534433T1 (en)
AU (1) AU2002233288B9 (en)
CA (2) CA2627862C (en)
WO (1) WO2002053170A2 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004104216A2 (en) * 2003-05-21 2004-12-02 Bayer Healthcare Ag Diagnostics and therapeutics for diseases associated with dipeptidylpeptidase iv (dpp4)

Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10025464A1 (en) * 2000-05-23 2001-12-06 Inst Medizintechnologie Magdeb Combined use of enzyme inhibitors for the therapy of autoimmune diseases, in transplants and tumor diseases, as well as combinations of pharmaceutical preparations comprising enzyme inhibitors
US7229969B2 (en) * 2001-01-02 2007-06-12 Imtm Gmbh Combinations of enzyme inhibitors and the use thereof
DE10100053A1 (en) * 2001-01-02 2002-08-22 Keyneurotek Ag I G Use of enzyme inhibitors of dipeptidyl peptidase IV and aminopeptidase N and pharmaceutical preparations therefrom for the prevention and / or therapy of ischemia-related acute and chronic neurodegenerative processes and diseases
US20030119036A1 (en) * 2001-10-31 2003-06-26 Millennium Pharmaceuticals, Inc. Methods of using 48149, a human aminopeptidase family member
DE10211555A1 (en) * 2002-03-15 2003-10-02 Imtm Inst Fuer Medizintechnolo Use of the inhibitors of enzymes with activities of the aminopeptidase N and / or the dipeptidyl peptidase IV and pharmaceutical preparations thereof for the therapy and prevention of dermatological diseases with sebocytic hyperproliferation and changed differentiation states
TW200404796A (en) * 2002-08-19 2004-04-01 Ono Pharmaceutical Co Nitrogen-containing compound
WO2004104575A2 (en) * 2003-05-23 2004-12-02 Bayer Healthcare Ag Diagnostics and therapeutics for diseases associated with x-prolyl aminopeptidase 2 (xpnpep2)
DE10330842A1 (en) * 2003-07-08 2005-02-10 Institut für Medizintechnologie Magdeburg GmbH, IMTM Use of the inhibitors of enzymes with activities of aminopeptidase N and / or dipeptidyl peptidase IV and pharmaceutical preparations thereof for the therapy and prevention of dermatological diseases with hyperproliferation and altered differentiation states of fibroblasts
US7169926B1 (en) 2003-08-13 2007-01-30 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
US7678909B1 (en) 2003-08-13 2010-03-16 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
DE10348022A1 (en) * 2003-10-15 2005-05-25 Imtm Gmbh New dipeptidyl peptidase IV inhibitors for the functional influence of different cells and for the treatment of immunological, inflammatory, neuronal and other diseases
DE10348023A1 (en) * 2003-10-15 2005-05-19 Imtm Gmbh New alanyl aminopeptidase inhibitors for the functional manipulation of different cells and for the treatment of immunological, inflammatory, neuronal and other diseases
DE10348044A1 (en) 2003-10-15 2005-05-19 Imtm Gmbh Dual alanyl aminopeptidase and dipeptidyl peptidase IV inhibitors for the functional influence of different cells and for the treatment of immunological, inflammatory, neuronal and other diseases
US7732446B1 (en) 2004-03-11 2010-06-08 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
US7687638B2 (en) 2004-06-04 2010-03-30 Takeda San Diego, Inc. Dipeptidyl peptidase inhibitors
WO2006019965A2 (en) 2004-07-16 2006-02-23 Takeda San Diego, Inc. Dipeptidyl peptidase inhibitors
EP1702916A1 (en) * 2005-03-18 2006-09-20 Santhera Pharmaceuticals (Schweiz) GmbH DPP-IV inhibitors
WO2006116157A2 (en) 2005-04-22 2006-11-02 Alantos Pharmaceuticals Holding, Inc. Dipeptidyl peptidase-iv inhibitors
SI1942898T2 (en) 2005-09-14 2014-08-29 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors for treating diabetes
CN102675221A (en) 2005-09-16 2012-09-19 武田药品工业株式会社 Intermediate in method for preparing pyrimidinedione derivative
DE102005054700B4 (en) 2005-11-16 2009-01-08 Imtm Gmbh New dual peptidase inhibitors as prodrugs for the treatment of inflammatory and other diseases
WO2007112347A1 (en) 2006-03-28 2007-10-04 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
US8324383B2 (en) 2006-09-13 2012-12-04 Takeda Pharmaceutical Company Limited Methods of making polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile
TW200838536A (en) 2006-11-29 2008-10-01 Takeda Pharmaceutical Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor
US8093236B2 (en) 2007-03-13 2012-01-10 Takeda Pharmaceuticals Company Limited Weekly administration of dipeptidyl peptidase inhibitors
US8524654B2 (en) * 2007-05-21 2013-09-03 The Uab Research Foundation Prolyl endopeptidase inhibitors for reducing or preventing neutrophilic inflammation
DE102007039429A1 (en) * 2007-08-21 2009-02-26 Imtm Gmbh Method for activating regulatory T cells
EP2292589A1 (en) 2009-09-02 2011-03-09 IMTM GmbH Novel multifunctional peptidase inhibitors, especially for medical use
EP2506827B1 (en) 2009-11-30 2013-07-31 Inoflex AB Lubricious Aqueous Composition
EP2366394A1 (en) 2010-03-17 2011-09-21 IMTM GmbH Characterization and validation of inhibitors and ligands of dipeptidyl aminopeptidase IV (DP IV)
EP2418196A1 (en) * 2010-07-29 2012-02-15 IMTM GmbH Dual alanyl-aminopeptidase and dipeptidyl-peptidase IV inhibitors
GR1008310B (en) * 2013-10-03 2014-10-02 Εκεφε Δημοκριτος, Phoshinic pseudopeptide derivatives for potent inhibition of aminopeptidases of the oxytocinase subfamily of m1 aminopeptidases
JP2018507914A (en) 2015-03-09 2018-03-22 インテクリン・セラピューティクス・インコーポレイテッド Method for the treatment of non-alcoholic fatty liver disease and / or lipodystrophy
BR112019020485A2 (en) 2017-04-03 2020-05-12 Coherus Biosciences, Inc. PPARY AGONIST FOR TREATMENT OF PROGRESSIVE SUPRANUCLEAR PALSY

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DD296075A5 (en) 1989-08-07 1991-11-21 Martin-Luther-Universitaet Halle-Wittenberg,De PROCESS FOR THE PREPARATION OF NEW INHIBITORS OF DIPEPTIDYL PEPTIDASE IV
US5902790A (en) * 1995-10-03 1999-05-11 Cytran, Inc. Pharmaceutical angiostatic dipeptide compositions and method of use thereof
US6429212B1 (en) 1996-08-16 2002-08-06 Ishihara Sangyo Kaisha Ltd. Medicinal composition
JPH10218789A (en) 1996-12-06 1998-08-18 Nippon Kayaku Co Ltd Activator for aids vaccine containing ubenimex as active ingredient
WO1998044923A1 (en) * 1997-04-10 1998-10-15 Sloan-Kettering Institute For Cancer Research Anti-neoplastic effects of actinonin
AU3034299A (en) * 1998-03-09 1999-09-27 Fondatech Benelux N.V. Serine peptidase modulators
DE19826972A1 (en) 1998-06-18 1999-12-23 Univ Magdeburg Tech Inhibiting keratinocyte activation and proliferation, for treatment of dermatological disorders such as psoriasis or actinic precancerous states
CA2339537A1 (en) 1998-08-21 2000-03-02 Barbara Wallner Regulation of substrate activity
DE10025464A1 (en) * 2000-05-23 2001-12-06 Inst Medizintechnologie Magdeb Combined use of enzyme inhibitors for the therapy of autoimmune diseases, in transplants and tumor diseases, as well as combinations of pharmaceutical preparations comprising enzyme inhibitors
US7229969B2 (en) * 2001-01-02 2007-06-12 Imtm Gmbh Combinations of enzyme inhibitors and the use thereof

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004104216A2 (en) * 2003-05-21 2004-12-02 Bayer Healthcare Ag Diagnostics and therapeutics for diseases associated with dipeptidylpeptidase iv (dpp4)
WO2004104216A3 (en) * 2003-05-21 2005-03-03 Bayer Healthcare Ag Diagnostics and therapeutics for diseases associated with dipeptidylpeptidase iv (dpp4)

Also Published As

Publication number Publication date
CA2436724C (en) 2010-03-16
JP2004520330A (en) 2004-07-08
AU2002233288B2 (en) 2005-10-20
US20040132639A1 (en) 2004-07-08
US7803776B2 (en) 2010-09-28
WO2002053170A3 (en) 2003-02-20
CA2627862C (en) 2009-12-22
CN100579582C (en) 2010-01-13
CN1484533A (en) 2004-03-24
US20070249541A1 (en) 2007-10-25
AU2002233288B9 (en) 2007-08-09
ATE534433T1 (en) 2011-12-15
EP1349576B1 (en) 2011-11-23
EP1349576A2 (en) 2003-10-08
WO2002053170A2 (en) 2002-07-11
CA2627862A1 (en) 2002-07-11
US7229969B2 (en) 2007-06-12

Similar Documents

Publication Publication Date Title
CA2436724A1 (en) Use of inhibitors of dipeptidyl peptidase iv (dp iv) in combination with inhibitors of alanyl-aminopeptidase (apn)
JP2004520330A5 (en)
CA2410305A1 (en) Preparations comprising combinations of enzyme inhibitors, and the use thereof
JP2003534293A5 (en)
EP0471651A2 (en) Peptide boronic acid derivatives having protease inhibiting activity
EP0736036B1 (en) Kininogen inhibitors
AU2003214105B2 (en) Use of enzyme inhibitors with aminopeptidase N and/or dipeptidylpeptidase IV activities and pharmaceutical preparations produced therefrom for the therapy and prevention of dermatological diseases with seborrhoeic hyperproliferation and altered differentiation states
US20070042938A1 (en) Use of dpiv and apn inhibitors for the treatment of dermatalogical diseases involving the hyperproliferation and modified differentiation conditions of fibroblasts
Brömme et al. Enzyme-substrate interactions in the hydrolysis of peptides by cathepsins B and H from rat liver
Savory et al. Reaction of proteasomes with peptidylchloromethanes and peptidyldiazomethanes
EP0922054A1 (en) Anticoagulant peptidyl-arginine aldehyde derivatives
Midura-Nowaczek et al. Synthesis of alkylamides of dipeptides as potential plasmin inhibitors
Purwin et al. Short peptides containing L-lysine and e-aminocaproic acid as potential plasmin inhibitors
Markowska et al. Low molecular peptides as potential inhibitors of plasmin
DE10102392A1 (en) Inhibiting DNA synthesis in T-lymphocytes, keratinocytes and TH2 cytokine production, comprises combined administration of dipeptidyl peptidase and alanyl-aminopeptidase inhibitors
Patterson Inhibition by bestatin of a mouse ascites tumor dipeptidase: Reversal by certain substrates
DE10155093A1 (en) Inhibiting DNA synthesis in T-lymphocytes, keratinocytes and TH2 cytokine production, comprises combined administration of dipeptidyl peptidase and alanyl-aminopeptidase inhibitors

Legal Events

Date Code Title Description
EEER Examination request
MKLA Lapsed

Effective date: 20131223